ACP InternistWeekly

In the News for the Week of March 27, 2012

Highlights

Guideline issued on acute bacterial rhinosinusitis

The Infectious Diseases Society of America (IDSA) issued a new guideline last week on the diagnosis and management of acute
bacterial rhinosinusitis, offering ways to distinguish bacterial from viral infection and stressing that antibiotic treatment
is not necessary in the latter case. More...

Daily aspirin may reduce cancer incidence, prevent metastases

Three related studies bolster the case for daily aspirin for cancer prevention, indicating that it may have a preventive effect
after three years, as well as reduce future metastases, while having little impact on increased bleeding risk in the long
term. More...

Test yourself

MKSAP Quiz: Migraine associated with menstruation

This week's quiz asks readers to determine the appropriate treatment for a 36-year-old woman with migraine associated with
menstruation. More...

Hypertension

Patients with hypertension who have a between-arm difference of at least 10 mm Hg in systolic blood pressure may be at higher
risk for cardiovascular events and death, according to a new study. More...

Internal Medicine 2012

Fellowship consultation sessions available

ACP Job Placement Center calls for job seekers' profiles

Physicians looking for a new job may submit a job seeker's profile to the ACP Job Placement Center, a service available at
Internal Medicine 2012. More...

Cartoon caption contest

Put words in our mouth

ACP InternistWeekly wants readers to create captions for our new cartoon and help choose the winner. Pen the winning caption and win a $50 gift
certificate good toward any ACP product, program or service. More...

Physician editor: Daisy Smith, MD, FACP

Highlights

Guideline issued on acute bacterial rhinosinusitis

The Infectious Diseases Society of America (IDSA) issued a new guideline last week on the diagnosis and management of acute
bacterial rhinosinusitis, offering ways to distinguish bacterial from viral infection and stressing that antibiotic treatment
is not necessary in the latter case.

The guideline was developed by an 11-member multidisciplinary expert panel that included representatives from several organizations,
including ACP. It is the IDSA's first guideline on this topic and is intended for primary care physicians, especially those
who see patients in community settings or in emergency departments.

The guideline describes the characteristics of bacterial versus viral sinus infections to help clinicians better differentiate
between the two. Antibiotics are not recommended for most sinus infections because 90% to 98% are caused by viruses, the guideline
said.

An infection probably has a bacterial cause and warrants antibiotics if symptoms last for at least 10 days and are not improving;
if symptoms are severe, such as a temperature of at least 102° and facial pain for three to four successive days; and
if symptoms worsen, usually after a viral upper respiratory infection of five or six days' duration that seemed to be improving,
according to the guideline.

In patients who do have a bacterial sinus infection, the guideline recommends amoxicillin-clavulanate rather than amoxicillin
alone, because clavulanate (a β-lactamase inhibitor) will improve the coverage of both ampicillin-resistant Haemophilus influenzae and Moraxella catarrhalis. Common antibiotics such as azithromycin, clarithromycin and trimethoprim-sulfamethoxazole are not recommended because of
resistance issues. The guideline also recommends that antibiotic treatment in adults last five to seven days rather than 10
days to two weeks.

The full text of the guideline, which was published March 20 by Clinical Infectious Diseases, is available online.

Daily aspirin may reduce cancer incidence, prevent metastases

Three related studies bolster the case for daily aspirin for cancer prevention, indicating that it may have a preventive effect
after three years, as well as reduce future metastases, while having little impact on increased bleeding risk in the long
term.

The first study examined 51 randomized trials of daily aspirin versus no aspirin prescribed to prevent vascular events. All
the trials looked at death due to cancer, all non-vascular death, vascular death and all-cause deaths.

Primary prevention trials showed that a reduction in non-vascular deaths accounted for 87 (91%) of 96 deaths prevented. In
six trials of daily low-dose aspirin in primary prevention (35,535 participants), aspirin reduced cancer incidence from three
years onward (OR, 0.76; P=0.0003) in women (OR, 0.75; P=0.01) and in men (OR, 0.77; P=0.008).

The reduced risk of major vascular events on aspirin was initially offset by an increased risk of major bleeding, the authors
noted. But effects on both outcomes diminished with increasing follow-up, leaving only the reduced risk of cancer (absolute
reduction, 3.13 per 1,000 patients per year) from three years onward. Case-fatality from major extracranial bleeds was also
lower with aspirin (OR, 0.32; P=0.009).

The authors noted that aspirin reduced cancer deaths by nearly 40% after five years, reduced the risk of all vascular death,
reduced the incidence of cancer by 25% after three years, and reduced cancer incidence in women.

"The demonstration of overall benefit from aspirin in the shorter-term, and the finding that the increased risk of major extracranial
bleeding does not persist with extended use, add to the case for long-term use of aspirin for cancer prevention in middle
age, in addition to appropriate dietary and lifestyle interventions," the authors concluded.

The second study indicated that, as well as reducing the long-term risk of some cancers, aspirin also prevents distant cancer
metastases. It included five large randomized trials of 75 mg or more of daily aspirin for the prevention of vascular events.

Of 17,285 trial participants, 987 had a new solid cancer diagnosed during mean in-trial follow-up of 6.5 years. Aspirin reduced
risk of cancer with distant metastasis (all cancers, hazard ratio [HR], 0.64; P=0.001; adenocarcinoma, HR, 0.54; P=0.0007; and other solid cancers, HR, 0.82; P=0.39). The reduction was mainly due to a reduction in proportion of adenocarcinomas that were metastatic versus local (OR,
0.52; P=0.0006).

Aspirin reduced risk of adenocarcinoma with metastasis at initial diagnosis (HR, 0.69; P=0.02) and risk of metastasis on subsequent follow-up in patients without metastasis initially (HR, 0.45; P=0.0009), particularly in patients with colorectal cancer (HR, 0.26; P=0.0008) and in patients who remained on trial treatment up to or after diagnosis (HR, 0.31; P=0.0009). Aspirin reduced death due to cancer in patients who developed adenocarcinoma, particularly in those without metastasis
at diagnosis (HR, 0.50; P=0.0006).

That aspirin prevents distant metastasis could account for the early reduction in cancer deaths in trials of daily aspirin
versus control, the authors wrote.

The third study compared outcomes for observational versus randomized trials. Observational studies suggest that regular use
of aspirin is associated with a reduction in the long-term risk of several cancers and the risk of distant metastasis. Colorectal
cancer was used as the test case in this study.

In case-control studies, regular use of aspirin was associated with reduced risk of colorectal cancer (pooled OR, 0.62; P<0.0001, 17 studies), with little heterogeneity (P=0.13) in effect between studies, and good agreement with the effect of daily aspirin use on 20-year risk for death due to
colorectal cancer from the randomized trials (OR, 0.58; P=0.0002; P=0.45 for heterogeneity). Similarly consistent reductions were seen in risks of esophageal, gastric, biliary and breast cancer.

Overall, estimates of the effect of aspirin on individual cancers in case-control studies were highly correlated with those
in randomized trials (r2=0.71; P=0.0006), with largest effects on risk of gastrointestinal cancers (case-control studies, OR, 0.62; P<0.0001, 41 studies; randomized trials, OR, 0.54; P<0.0001).

Estimates of effects in cohort studies were similar when analyses were stratified by frequency and duration of aspirin use,
were based on updated assessments of use during follow-up, and were appropriately adjusted for baseline characteristics.

"We now have shown that case-control studies yield estimates of the effect of aspirin on risk of colorectal cancer that are
in close agreement with those from the trials," the authors wrote.

An online commentary pointed out that the studies "show quite convincingly that aspirin seems to reduce cancer incidence and death across different
subgroups and cancer sites, with an apparent delayed effect. Additionally, aspirin's known benefits in vascular disease and
known toxic effects in causing major bleeding emerged in the short term, but diminished over time. Thus, for most individuals,
the risk-benefit calculus of aspirin seems to favour aspirin's long-term anticancer benefit."

Test yourself

MKSAP Quiz: Migraine associated with menstruation

A 36-year-old woman is evaluated in the office for a history of migraine, with and without aura, since age 16 years. She has
an average of three attacks each month and consistently experiences an attack 2 days prior to menstruation; this headache
is more difficult to treat than those not associated with menstruation. Although she typically obtains pain relief within
2 hours of taking sumatriptan, the headache recurs within 24 hours after each dose during the period of menstrual flow. Sumatriptan,
orally as needed, is her only medication.

Results of physical examination are unremarkable.

Which of the following is the most appropriate perimenstrual treatment for this patient's headaches?

The intent of the study was to determine whether a difference in SBP readings between arms could predict long-term survival.
Blood pressure measurements were obtained in both arms at three consecutive visits. The study's main outcome measures were
cardiovascular events and all-cause mortality over a median of 9.8 years of follow-up. The results were published online March 20 by BMJ.

At study entry, 55 of 230 participants (24%) had a mean interarm SBP difference of at least 10 mm Hg and 21 of 230 (9%) had
a difference of at least 15 mm Hg, while 14 of 230 patients (6%) had a mean interarm difference in diastolic blood pressure
(DBP) of at least 10 mm Hg. An association was noted between the two mean SBP differences and all-cause mortality (adjusted
hazard ratios, 3.6 [95% CI, 2.0 to 6.5] and 3.1 [95% CI, 1.6 to 6.0], respectively).

One hundred eighty-three patients without preexisting cardiovascular disease but with an SBP difference of at least 10 mm
Hg or at least 15 mm Hg between arms also had an increased risk for death (adjusted hazard ratio, 2.6 [95% 1.4 to 4.8] and
2.7 [95% CI, 1.3 to 5.4], respectively). A 10-mm Hg interarm difference in DBP had a weak association with increased risk
for death or cardiovascular events.

The authors noted that the sequence in which each arm was measured was not randomized, and that their data came from only
one practice, among other limitations. However, they concluded that different SBP readings between arms could indicate a long-term
risk for death or cardiovascular events in patients with hypertension.

"Assessment of blood pressure in both arms is recommended by guidelines and should become a core component of initial blood
pressure measurement in primary care," they wrote. "Detection of an interarm difference should prompt consideration of further
vascular assessment and aggressive management of risk factors."

An accompanying editorial pointed out that the authors averaged a single set of sequential blood pressure measurements instead of obtaining repeated
simultaneous measurements, which could have led to misclassification of patients whose blood pressure was highly variable.
This, along with other study limitations, means that the findings are not definitive and need to be replicated, the editorialist
wrote. He added that future studies should also compare interarm differences in blood pressure with known predictors of death
from cardiovascular disease.

However, the editorialist recommended that clinicians follow current guidelines and measure blood pressure in both arms to
detect patients with a difference of at least 10 mm Hg, in whom the positive predictive value for peripheral vascular disease
is high.

"A sequential measurement, followed by confirmation with at least two simultaneous measurements using two automatic devices,
seems to be a reasonable approach. The optimal number of repeated measurements and monitoring intervals are unknown," he wrote.

Venous thromboembolism

Fixed-dose oral rivaroxaban is as effective as standard anticoagulant
therapy for pulmonary embolism (PE) and may have a lower bleeding risk,
a new study found.

Researchers conducted a four-year, randomized, open-label noninferiority trial with 4,832 patients who had acute symptomatic
PE with or without deep vein thrombosis (DVT). Patients came from 263 sites in 38 countries.

Half received 15 mg of rivaroxaban twice a day for three weeks, followed by 20 mg once daily. The other, "standard therapy"
patients received enoxaparin at a dose of 1.0 mg per kilogram of body weight twice daily, plus warfarin or acenocoumarol.
Treatment lasted for three, six, or 12 months, with duration determined by the treating physician before randomization.

The primary efficacy outcome was symptomatic recurrent venous thromboembolism (VTE), and the primary safety outcome was a
first major or clinically relevant nonmajor bleeding event. The study was supported by Bayer Healthcare and Janssen Pharmaceuticals.

There were 50 symptomatic recurrent VTE events in the rivaroxaban group (2.1%), which was noninferior to the 44 events in
the standard therapy group (1.8%; hazard ratio [HR], 1.12; noninferiority margin, 2.0; P=0.003). The primary safety outcome occurred in 10.3% of rivaroxaban patients and 11.4% of standard-therapy patients (HR,
0.90; P=0.23). Major bleeding was seen in 26 patients (1.1%) in the rivaroxaban group and 52 patients (2.2%) in the standard-therapy
group (HR, 0.49; P=0.003). Rates of other adverse outcomes were similar between the two groups. Results were published online March 26 by the New England Journal of Medicine.

Study strengths included that the population represented the real-life spectrum of patients who present with symptomatic PE,
excluding those for whom fibrinolysis is planned, the authors said. Nearly 25% had extensive disease, and nearly 25% had concomitant
symptomatic DVT, for example.

The study's open design may have caused a slight diagnostic-suspicion bias against rivaroxaban. There was a higher number
of suspected VTE events in the rivaroxaban group than in the enoxaparin group, yet confirmed event rates were similar.

Overall, this study's findings, combined with the authors' previous study in DVT patients, "support the use of rivaroxaban
as a single oral agent for patients with (VTE)," they said. The fixed-dose regimen will simplify treatment by obviating the
need for laboratory monitoring that accompanies standard therapy, they said.

Imaging

A think tank of cardiovascular imaging stakeholders developed a consensus plan on several broad directions for ensuring patient
safety in an era of increased medical radiation.

Physicians need to perform only appropriate and necessary diagnostic exams and procedures, consider exams or procedures without
radiation, and use the best possible combination of equipment, doses and protocols, according to a report written by a collaboration
of eight medical societies and Duke University Clinical Research Institute.

The four critical areas covered by the plan are as follows:

Quantifying the estimated risks of malignancies that may occur much later from low-dose radiation of cardiovascular imaging
and therapies;

Measuring and reporting radiation dose in cardiovascular imaging and procedures;

Minimizing radiation dose for single episodes of care and across entire systems of care; and

Educating and communicating with multiple groups to increase awareness and achieve goals in minimizing exposure.

The full text of the report was published online March 22 by the Journal of the American College of Cardiology and will appear in print in the May 15 issue, as well as in an upcoming issue of Circulation: Journal of the American Heart Association.

Internal Medicine 2012

Fellowship consultation sessions available

ACP is offering several "Advancement to Fellowship" consultation sessions at Internal Medicine 2012.

The sessions will be held at 10:30 a.m. on Thursday, April 19, and at 10:30 a.m. and 3:45 p.m. on Friday, April 20, at the
Membership Booth in the ACP Resource Center (Booth 1039 in the Exhibit Hall). Each session will be led by Capt. Jeffrey B.
Cole, MC, USN, FACP, chair of ACP's Credential Committee. The Friday afternoon session is intended especially for international
members, and Spanish-speaking staff will be present to translate information and questions. Fellowship application materials
will be available for all eligible members.

ACP Job Placement Center calls for job seekers' profiles

Physicians looking for a new job may submit a job seeker's profile to the ACP Job Placement Center, a service available at
Internal Medicine 2012, to be held April 19-21 in New Orleans. The Center, located in the New Orleans Ernest N. Morial Convention
Center, Booth 430, provides physicians with tools to assist in job searches as well as the opportunity to meet with potential
employers.

Profiles will be included in one of two booklets based on job seekers' criteria and distributed only to Job Placement Center
sponsors and exhibitors who have submitted a job posting. After reviewing a profile, a recruiter may contact the physician
to schedule a private on-site interview at the Center. Profiles can be submitted online.

Cartoon caption contest

Put words in our mouth

ACP InternistWeekly wants readers to create captions for this cartoon and help choose the winner. Pen the winning caption and win a $50 gift certificate
good toward any ACP product, program or service.

E‑mail all entries to acpinternist@acponline.org. ACP staff will choose finalists and post them online for an online vote by readers. The winner will appear in an upcoming
edition.

MKSAP Answer and Critique

The correct answer is B) Mefenamic acid. This item is available to MKSAP 15 subscribers as item 3 in the Neurology section.
More information about MKSAP 15 is available online.

This patient should be treated with mefenamic acid. She has migraine with aura, migraine without aura, and menstrually related
migraine. Her menstrually related headaches are less responsive to acute therapy than are the non-menstrually related attacks,
and headache recurs daily throughout menses. The best management for this patient is, therefore, the perimenstrual use of
a prophylactic agent. There is evidence that supports the use of mefenamic acid for perimenstrual prophylaxis, with treatment
starting 2 days prior to the onset of flow or 1 day prior to the expected onset of the headache and continuing for the duration
of menstruation. In this patient, that would mean beginning 3 days before the onset of menstrual flow and continuing throughout
menstruation.

The use of combined oral contraceptive therapy (estrogen plus progestin) is contraindicated in this woman because of her history
of migraine with aura. Women with migraine with aura are at a twofold increased risk of ischemic stroke, ischemic myocardial
infarction, and venous thromboembolism. The risk of stroke is increased further, up to eightfold, in women with migraine with
aura who use combined oral contraceptive pills.

No evidence supports the oral use of either sumatriptan plus naproxen sodium or topiramate for the perimenstrual prophylaxis
of menstrually related migraine. Similarly, there is no evidence supporting the subcutaneous use of sumatriptan in this setting.
In fact, the higher recurrence rate with the subcutaneous formulation may prove counterproductive.

Key Point

Evidence supports the use of mefenamic acid for perimenstrual prophylaxis of menstrually related migraines, with treatment
starting 2 days prior to the onset of flow or 1 day prior to the expected onset of the headache and continuing for the duration
of menstruation.

Test yourself

A 54-year-old woman is evaluated for shortness of breath of 3 months' duration and a 4.5-kg (10-lb) weight loss over the preceding 2 months. She has a 35-pack-year smoking history. Following a physical exam and further testing, what is the most appropriate treatment?

Internal Medicine Meeting 2015 Live Simulcast!

Unable to attend the meeting this year? On Saturday, May 2, seven sessions will be streamed live from the meeting. Register for the simulcast and earn CME credit after watching each session. Watch it live or download for later viewing.

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